Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative

Abstract

Background Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question “Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?” Methods The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS). Results Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests. Conclusions The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).

A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer

“…Although according to interim analysis of RxPONDER trial, the guideline recommends Oncotype DX for same subset of patients, however the interpretation of the results in premenopausal patients is complex 13 . The use of genomic signatures is recommended for this subset of patients by national and international clinical guidelines, i.e., St. Gallen Consensus Conference, European Society for Medical Oncology (ESMO), and American Society of Clinical Oncology 8 , 14 , 15 . However, the economic burden on patients makes clinicians hesitate to recommend genomic testing.…”

“…Genomic analysis would be useful to make a decision in this subgroup of breast cancer patients with intermediate risk of prognostic clinical factors. Most of the breast cancer guidelines introduces to consider several genomic assays regarding the use of adjuvant chemotherapy 5 – 8 . MammaPrint (MMP), a 70-gene-signature‒based test is available for patients with HR + and minimal nodal involvement (N0-1).…”

Comparison of Genomic Profiling Data with Clinical Parameters: Implications for Breast Cancer Prognosis

“…These findings agree with other reports, for example, in the MINDACT study, 46.2% of the patients at clinical high risk were classified by MammaPrint as genomic low risk [ 5 ], while a Dutch study reported that MammaPrint classified 52.6% of clinical high-risk tumors as genomic low risk [ 18 ], supporting de-escalation. Recent guidelines suggest the use of the 70-gene signature only for women at high clinical risk [ 37 ]. However, although the agreement of clinical low risk with genomic data were high, 20% of cases displayed genomic high risk, implying that these patients would not receive the required therapy, and thus possibly resulting in their under-treatment.…”

Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?

“…On this point, Gomez HL et al reported that up to 70% of HR (+) and N0 ESBC patients with RS ≤ 25 may not need ACT [ 16 ]. Since the inconsistencies in risk prediction exist among the genome tests, the European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group suggests the use of Oncotype DX for N0 breast cancer patients, and the use of MammaPrint for women at high clinical risk [ 9 ].…”

“…However, some ESBC patients with ER+ and HER2− may have received unnecessary ACT, and those with a low risk of cancer recurrence may avoid ACT [ 8 ]. Thus, accurate prediction of the recurrence risk and response to ACT in patients with ESBC is crucial in order to optimize ACT [ 9 ].…”